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Endo > SM_189b: Calcium / Parathyroid / Bone Basic > Flashcards

SM_189b: Calcium / Parathyroid / Bone Basic Flashcards

1
Q

Describe the functions of Ca

A

Ca functons

  • Regulation of excitable tissues
  • Secretion
  • Coagulation
  • Enzymatic activity
  • Signal transduction
  • Formation and maintenance of the skeleton
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2
Q

Hypocalcemia results in ___

A

Hypocalcemia results in increased neuromuscular excitability

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3
Q

Hypercalcemia results in ___, ___, ___, ___, ___, and ___

A

Hypercalcemia results in dehydration, renal stones, pain, weakness, confusion, and cardiac arrhythmias

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4
Q

Normal serum Ca is ___

A

Normal serum Ca is 8.5-10.4 mg/dL

  • Serum Ca generally fluctuates no more than 0.2 mg/dL in either direction throughout the day
  • Tight homeostatic control is a consequence of feedback regulation between Ca and PTH
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5
Q

Calcium and PTH have an ___ effect

A

Calcium and PTH have an opposing effect

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6
Q

Most serum Ca is ___

A

Most serum Ca is ionized

  • Ionized (50%): mediates biological responses
  • Complex with anions (10%): phosphate, citrate
  • Protein bound (40%): 90% with albumin, remainder with globulins
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7
Q

Intestinal Ca absorption is promoted by ____ and ____

A

Intestinal Ca absorption is promoted by facilitated diffusion through the small intestin and Vitamin D dependent transport of Ca and P

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8
Q

Calcium loss through the intestine can result from ____, ____, and ____

A

Calcium loss through the intestine can result from

  • Glucocorticoids: decrease Ca absorption
  • Mucosal and biliary secretion
  • Steatorrhea, diarrhea, and malabsorption syndromes
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9
Q

Ca absorption is increased by ____

A

Ca absorption is increased by PTH

(at distal nephron)

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10
Q

Calcium excretion is increased by ____, ____, and ____

A

Calcium excretion is increased by loop diuretics, dietary protein, and glucocorticoids

Loop diuretics (furosemide, ethacrynic acid)

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11
Q

Thiazide diuretics ____ calcium excretion

A

Thiazide diuretics decrease calcium excretion

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12
Q

Phosphate excretion is increased by ____ and ____

A

Phosphate excretion is increased by PTH and FGF-23

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13
Q

___ is major site of Ca storage in the body

A

Bone is major site of Ca storage in the body

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14
Q

Describe Ca handling in bone

A

Ca handling in bone

  • Bone is major site of Ca storage in body: Ca stored largely in a crystalline form resembling hydroxyapatite
  • Stable pool is regulated by cellular activity, affected by hormones, cytokines, growth factors, and drugs
  • Exchangeable pool provides buffering and acid-base balance
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15
Q

Describe roles of bone

A

Roles of bone

  • Metabolic: Ca homeostasis, buffering
  • Structural: supports body, protects internal organs
  • Cell development and maturation: bone marrow is site of hematopoiesis, provides bone cell precursors, and produces cytokines that affect bone
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16
Q

Appendicular bone is ___

A

Appendicular bone is largely compact cortical bone with some trabecular regions

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17
Q

Axial bone is ____

A

Axial bone is thin cortex, largely trabecular, and highly connected bony plates

  • Contains more marrow and fat
  • Trabecular bone has highest activity
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18
Q

Ca is regulated in the ____, ____, and ____

A

Ca is regulated in the intestine, kidney, and bone

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19
Q

Osteoclasts secrete ____ and ____ to ____

A

Osteoclasts secrete H+ and proteolytic enzymes to degrade bone

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20
Q

RANKL / TRANCE is a ____ produced by ____

A

RANKL / TRANCE is a membrane-associated cytokine produced by osteoblasts and other cells

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21
Q

RANKL acts on the ___ receptor on osteoclasts and osteoclast precursors

A

RANKL acts on the RANKL receptor on osteoclasts and osteoclast precursors

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22
Q

RANKL promotes ____, ____, ____, and ____

A

RANKL promotes fusion, differentiation, activity, and survival of osteoclasts

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23
Q

Osteoblasts secrete ____, ____, ____, and ____

A

Osteoblasts secrete collagen, other matrix proteins, growth factors, and cytokines

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24
Q

____ is 90% of the protein of the boen matrix (osteoid)

A

Collagen is 90% of the protein of the boen matrix (osteoid)

  • Osteiod + hydroxyapatite = mineralized matrix
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25
Q

____, ____, and ____ are products used as markers of osteoblastic activity

A

Osteocalcin, alkaline phosphatase, and collagen peptides cleaved off during synthesis are products used as markers of osteoblastic activity

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26
Q

____, ____, and ____ are osteoblast products that affect osteoclasts

A

Selected cytokines (IL-6), RANKL, and osteoprotegerin (RANKL antagonist) are osteoblast products that affect osteoclasts

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27
Q

____ are the source of osteoblasts

A

Pluripotent precursors are the source of osteoblasts

(can also give rise to adipocytes, chondrocytes, and myocytes)

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28
Q

____, ____, and ____ promote osteoblast differentiation and activity

A

Wnt signaling, insulin-like growth factor 1, and bone morphogenic proteins promote osteoblast differentiation and activity

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29
Q

Osteoblasts become ____ as bone forms around the osteoblasts

A

Osteoblasts become osteocytes as bone forms around the osteoblasts

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30
Q

Describe osteocytes

A

Osteocytes

  • Comprise 90% of the cells of bone
  • Sense mechanical load
  • Connect with other cells of bone
  • Produce sclerostin (protein) that inhibits wnt signaling and osteoblast differentiation
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31
Q

Sclerostin is produced by ____ and inhibits ____ and ____

A

Sclerostin is produced by osteocytes and inhibits wnt signaling and osteoblast differentiation

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32
Q

Sclerostin ____ increase bone formation

A

Sclerostin antagonists increase bone formation

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33
Q

Bone remodeling activity is ____ and involves ____

A

Bone remodeling activity is continual and involves sequential activity of osteoclasts and osteoblasts

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34
Q

Osteoporosis is ____

A

Osteoporosis is a systematic condition in which osteoblastic activity cannot keep pace with accelerated osteoclastic activity, resulting in the loss of mineral and matrix and increased susceptibility to fracture

35
Q

Paget’s disease of bone is ___

A

Paget’s disease of bone is a disorder in which locally increased osteoclastic activity is followed by increased osteoblastic activity, resulting in abnormal bone

36
Q

Vitamin D is ___

A

Vitamin D is a secosteroid produced in the skin by action of UV light on 7-dehydrocholesterol

  • Vitamins D2 and D3 have differences in side chain
  • Vitamin D2 is produced by plants and fungi
  • Vitamin D3 is produced by animals
37
Q

Vitamin D is converted to ____ in the liver

A

Vitamin D is converted to 25-(OH)-D in the liver

38
Q

Final activation step for Vitamin D is ____ and occurs in the ____

A

Final activation step for Vitamin D is 1-hydroxylation and occurs in the kidney

  • Stimulated by PTH
  • Stimulated by low serum phosphate
  • Tightly feedback regulated
39
Q

Active metabolite of Vitamin D3 is ____

A

Active metabolite of Vitamin D3 is 1,25(OH)2D3 (calcitriol)

  • Considered a hormone / endocrine because it is synthesized at one site in the body and travels through the bloodstream to target sites
40
Q

Describe calcitriol actions

A

Calcitriol actions

  • Effects produced through nuclear receptors
  • Stimulates intestinal Ca and P absorption -> bone mineralization
  • Suppresses PTH secretion
41
Q

In excess, calcitriol can cause ____ through ____ and ____

A

In excess, calcitriol can cause hypercalcemia through excess Ca and P absorption and direct actions on osteoblasts to increase RANKL

42
Q

Describe uses of Vitamin D

A

Vitamin D uses

  • Use related to its effects on Ca and P absorption
  • Treatment of nutritional rickets
  • Treatment of ricks and osteomalacia due to inadequate 1-hydroxylation of 25-OH-D: Vitamin D resistant rickets, VDRR, renal disease, and hypoparathyroidism
  • Adequate Vitamin D is important adjunct to other therapy in patients with osteoporosis
43
Q

Describe Vitamin D analogues with unique properties

A

Vitamin D analogues with unique properties

  • Alphacalcidol (1alpha-hydroxyvitamin D3): does not require 1-hydroxylation, useful when 1-hydroxylase is deficient
  • Paracalcitol: suppresses PTH, minimal effects on intestine, useful for secondary hyperparathyroidism
  • Calcipotriol: effective topically, used for psoriasis
44
Q

Describe PTH

A

PTH

  • 84 amino acid peptide
  • Derived from a larger peptide by processing steps in the ER and Golgi
  • Normally secreted at least partially in a pulsatile manner
  • An analogue, 1-34 PTH (teriparatide), has full activity
45
Q

Calcium ____ regulates release of PTH via the ____

A

Calcium negatively regulates release of PTH via the Ca-sensing receptor

46
Q

Calcimimetics act on the ___ to reduce PTH secretion

A

Calcimimetics act on the Ca sensing receptor to reduce PTH secretion

47
Q

Calcitriol and analogs ____ release of PTH

A

Calcitriol and analogs inhibit release of PTH

48
Q

Cinacalcet is a ___

A

Cinacalcet is a calcimimetic

49
Q

Calcimimetics (Cinacalcet) act by ___ and ___

A

Calcimimetics (Cinacalcet) act by allosterically activating the CaSR and enhancing the sensitivity of CaSR

  • Enhanced sensitivity of CaSR: lowers [Ca] at which PTH is suppressed
50
Q

Cinacalcet is used to ____

A

Cinacalcet is used to suppress PTH in hyperparathyroidism or parathyroid carcinoma

  • Calcimemtic
  • Orally effective, metabolized by CYPs, renal excretion
  • Side effects: hypocalcemia, adynamic bone disease
51
Q

PTH acts through ____ in ____ and ____

A

PTH acts through GPCRs in bone (osteoblasts and osteocytes) and kidney

  • PKA and PKC pathways are stimulated
52
Q

PTH acts on the kidney to ___, ___, and ___

A

PTH acts on the kidney to

  • Increase Ca absorption
  • Decrease phosphate reabsorption
  • Stimulate 1alpha-hydroxylation of 25-OH-D to form 1,25-(OH)2D3
53
Q

PTH effects on the intestine are ____, mediated through the ____

A

PTH effects on the intestine are indirect, mediated through the increase in 1,25-(OH)2D3

54
Q

Bone ___ results from continuous exposure to PTH

A

Bone resorption results from continuous exposure to PTH

  • Resorption is largely due to increased RANKL
55
Q

Bone ___ results from intermittent exposure to PTH

A

Bone formation results from intermittent exposure to PTH

  • Mechanisms: decreased osteoblast apoptosis, increased osteoblast differentiation, and suppression of sclerostin production
56
Q

Teriparatide (PTH 1-34) is an ____ agent for the treatment of ____

A

Teriparatide (PTH 1-34) is an anabolic agent for the treatment of osteoporosis

  • Administered by subcutaneous injection only daily
  • Concerns: hypercalcemia, osteosarcoma (not seen in humans)
57
Q

Parathyroid hormone related peptide ____, ____, and ____

A

Parathyroid hormone related peptide is an etiologic factor in the hypercalcemia of malignancy and in osteolytic metastases of breast cancer, effects on mammary glands / placenta / smooth muscle, and anabolic actions on bone

  • Abaloparatide is PHTHrP analog
58
Q

Calcitonin is secreted by ____ after stimulation by ____

A

Calcitonin is secreted by C-cells of thryoid gland after stimulation by calcium

59
Q

Calcitonin acts on ____ through GPCRs to ____

A

Calcitonin acts on mature osteoclasts through GPCRs to inhibit bone resorption

  • Antiresorptive
  • Useful for Paget’s disease
60
Q

Fibroblast growth factor 23 is produced by ____ and ____ and its synthesis is increased by ____ and ____

A

Fibroblast growth factor 23 is produced by osteoblasts and osteocytes and its synthesis is increased by calcitriol and phosphate

61
Q

Fibroblast growth factor 23 functions to ___

A

Fibroblast growth factor 23 functions to inhibit renal calcitriol synthesis and phosphate reabsorption

62
Q

Describe pathophysiology resulting from low/high FGF-23

A

Pathophysiology resulting from low/high FGF-23

  • Tumoral calcinosis results from mutations that inhibit FGF 23 secretion
  • Hypophosphatemic rickets result from mutations in a cleavage site required for FGF 23 inactivation
63
Q

Estrogen is important for maintenance of ____

A

Estrogen is important for maintenance of bone

  • Decreased estrogen at menopause accelerates bone loss
64
Q

Estrogen is ____ and ____

A

Estrogen is antiresorptive and anabolic

  • Inhibits production of RANKL and IL-6
  • Increases production of osteoprotegerin
  • Causes apoptosis of osteoclasts
  • Decreases sclerostin, promoting bone formation
65
Q

Androgens are aromatized to ____ in bone and act on ____

A

Androgens are aromatized to estrogen in bone and act onestrogen receptors

66
Q

____ has been reported in males with aromatase deficiency or who lack estrogen receptors

A

Osteoporosis has been reported in males with aromatase deficiency or who lack estrogen receptors

67
Q

Raloxifene is a ___

A

Raloxifene is a selective estrogen response modulator

68
Q

Selective estrogen response modulators (raloxifene) interacts with ____

A

Selective estrogen response modulators (raloxifene) interacts with estrogen receptors in a tissue-specific manner

  • Estrogenic actions on bone (largely antiresorptive)
  • Anti-estrogenic effects on the mammary gland
69
Q

Selective estrogen response modulators (raloxifene) are used to ____ and ____

A

Selective estrogen response modulators (raloxifene) are used to prevent / treat postmenopausal osteoporosis and reduce risk of breast cancer

  • Adverse effects: thromboses (estrogenic), hot flashes (anti-estrogenic), contraindicated in women who may become pregnant
70
Q

Alendronate, risedronate, zoledronic acid, and ibandronate are ____

A

Alendronate, risedronate, zoledronic acid, and ibandronate are bisphosphonates

  • Analogs of pyrophosphate
71
Q

Bisphosphonates ___ and ___

A

Bisphosphonates accumulate in bone at sites of active resorption and inhibit osteoclast activity and survival after being taken up

  • Antiresorptive
  • Alendronate, risedronate, zoledronic acid, ibandronate
72
Q

Bisphosphonates are used to ____ and treat ____, ____, and ____

A

Bisphosphonates are used to prevent / treat osteoporosis and treat bone metastases from breast / prostate cancer, hypercalcemia, and Paget’s disease

73
Q

Describe adverse effects of bisphosphonates

A

Adverse effects of bisphosphonates

  • Heartburn, esophageal irritation, esophagitis
  • Abdominal pain, diarrhea
  • Osteonecrosis of the jaw and atypical femoral fractures are rare but serious
74
Q

Denosumab is a ____ that ____ and ____

A

Denosumab is a human monoclonal antibody against RANKL that inhibits osteoclast fusion, function, and survival (antiresorptive) and increases bone mineral density and decreases fractures

  • Used to treat osteoporosis
75
Q

Describe adverse effects of denosumab

A

Denosumab adverse effects

  • Hypocalcemia
  • Rashes
  • Osteonecrosis of jaw
  • Risk of infections in individuals with weak immune system
76
Q

Describe anti-resorptive therapy for osteoporosis

A

Anti-resorptive therapy for osteoporosis

77
Q

Describe formation-stimulating (anabolic) therapy for osteoporosis

A

Formation-stimulating (anabolic) therapy for osteoporosis

78
Q

___ and ___ are anabolic (bone formation) therapy for osteoporosis

A

PTH (teriparatide) and abaloparatide are anabolic (bone formation) therapy for osteoporosis

79
Q

Short term glucocorticoid treatment can reduce ____ through ____ and ____

A

Short term glucocorticoid treatment can reduce hypercalcemia through decreased intestinal calcium absorption and increased renal calcium excretion

80
Q

Chronic glucocorticoid treatment can cause ____

A

Chronic glucocorticoid treatment can cause osteoporosis

  • Decreased intestinal Ca absorption
  • Increase renal Ca excretion
  • Increase PTH secretion
  • Decrease gonadal steroids
  • Decrease protein synthesis in bone
81
Q

Hypocalcemia is treated with ____, ____, ____, and ____

A

Hypocalcemia is treated with Vitamin D, caclitriol, alphacalcidol, and thiazide diuretics

82
Q

Hypercalcemia is treated with ____, ____, ____, and ____

A

Hypercalcemia is treated with loop diuretics, bisphosphonates, calcitonin, and glucocorticoids

83
Q

Antiresorptive treatment for osteoporosis involves ____, ____, ____, ____, and ____

A

Antiresorptive treatment for osteoporosis involves bisphosphonates, denosumab, selective estrogen receptor modulators, estrogen, and calcitonin

(with Ca, Vitamin D, and exercise)

84
Q

Anabolic treatment for osteoporosis involves ____ and ____

A

Anabolic treatment for osteoporosis involves teriparatide (PTH) and abaloparatide (PTHrP analog)

(Ca, Vitamin D, and exercise)

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